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CN-122005854-A - Nano medicine delivery platform based on Zn/Co-MOF metal organic framework, and preparation method and application thereof

CN122005854ACN 122005854 ACN122005854 ACN 122005854ACN-122005854-A

Abstract

The invention provides a nano-drug delivery platform based on a Zn/Co-MOF metal organic framework, and a preparation method and application thereof, belonging to the technical field of biology and new medicines. The nano medicine delivery platform based on the Zn/Co-MOF metal organic framework comprises a Zn/Co-MOF metal organic framework core, an organic medicine composition loaded on the surface and micropores of the core and a homologous tumor cell membrane wrapped on the outermost layer, wherein the organic medicine composition comprises tamoxifen-cisplatin dimer prodrug, a photothermal therapeutic agent IR-820 and an immunomodulator metformin. The nano drug delivery platform provided by the invention monitors tumor development and treatment process in vivo through fluorescence luminescence visualization, integrates chemotherapy, photo-thermal and endocrine three modes into a whole, has good safety and biocompatibility, shows remarkable anti-tumor effect in a tumor-bearing nude mouse model, and provides a brand-new strategy for treating ER+ breast cancer.

Inventors

  • QIAO DAN
  • ZHU YUXUAN
  • ZHENG PENGWU
  • ZHANG JINZHENG
  • WU TIANYU
  • CHENG ZHENJIE

Assignees

  • 江西科技师范大学

Dates

Publication Date
20260512
Application Date
20260324

Claims (10)

  1. 1. A nano-drug delivery platform based on a Zn/Co-MOF metal organic framework is characterized by comprising a Zn/Co-MOF metal organic framework core, an organic drug composition loaded on the surface and micropores of the core and a homologous tumor cell membrane wrapped on the outermost layer; wherein the organic pharmaceutical composition comprises tamoxifen-cisplatin dimer prodrug, photo-thermal therapeutic agent IR-820 and immune modulator metformin.
  2. 2. The Zn/Co-MOF-based metal-organic framework nanodrug delivery platform of claim 1, wherein the Zn/Co-MOF metal-organic framework core is a hollow porous spherical structure with a diameter of 200-300nm.
  3. 3. The Zn/Co-MOF-based metal-organic framework nanodrug delivery platform of claim 1, wherein said tamoxifen-cisplatin dimer prodrug has the structural formula: 。
  4. 4. The Zn/Co-MOF-based metal-organic framework nanodrug delivery platform of claim 1, wherein said cognate tumor cell membrane is derived from MCF-7 cells.
  5. 5. A method of preparing a Zn/Co-MOF-based metal-organic framework nanodrug delivery platform as defined in any one of claims 1 to 4 comprising the steps of: (1) Reacting tamoxifen with 1-chloroacetyl chloride to generate an intermediate, esterifying with succinic anhydride, and finally coupling with oxidized cisplatin to obtain tamoxifen-cisplatin dimer prodrug; (2) Preparing Zn/Co-MOF nano particles; (3) The tamoxifen-cisplatin dimer prodrug, a photothermal therapeutic agent IR-820 and metformin are Co-assembled and loaded in the Zn/Co-MOF nano-particles to obtain drug-loaded nano-particles; (4) And (3) extracting MCF-7 cell membranes, and wrapping the MCF-7 cell membranes on the surfaces of the drug-carrying nano-particles obtained in the step (3) by a liposome extrusion method to obtain the Zn/Co-MOF-based nano-drug delivery platform of the metal organic framework.
  6. 6. The method of preparing a Zn/Co-MOF-based metal-organic framework nano-drug delivery platform of claim 5, wherein step (1) comprises the steps of: a. Dissolving tamoxifen in1, 2-dichloroethane, adding 1-chloroacetyl chloride at 0 ℃, continuously stirring, heating and refluxing, distilling under reduced pressure to remove solvent, and recrystallizing to obtain a compound 1, wherein the molar ratio of tamoxifen to 1-chloroacetyl chloride is 1:1, and the compound 1 has the structural formula: ; b. Dissolving the compound 1, 4-dimethylaminopyridine in dichloromethane, adding succinic anhydride at room temperature, stirring for reaction, and performing reduced pressure distillation and recrystallization after the reaction is finished to obtain a compound 2, wherein the molar ratio of the compound 1 to the succinic anhydride is 1:1, and the structural formula of the compound 2 is as follows: ; c. mixing cisplatin with H 2 O 2 uniformly, heating in a dark place, carrying out reflux reaction, cooling the reaction liquid overnight after the reaction is finished, centrifuging to remove supernatant, collecting separated pale yellow solid, and washing and vacuum drying to obtain a hydroxyplatinum compound 3, wherein the hydroxyplatinum compound 3 has the structural formula: ; d. Dissolving the compound 2 in anhydrous N, N-dimethylformamide, adding O- (benzotriazole-1-yl) -N, N, N ', N' -tetramethylurea tetrafluoroborate, stirring at room temperature, adding triethylamine, continuously stirring, adding the hydroxyplatinum compound 3, reacting under the protection of nitrogen atmosphere, and carrying out reduced pressure distillation and column chromatography separation after the reaction is finished to obtain the tamoxifen-cisplatin dimer prodrug, wherein the molar ratio of the compound 2 to O- (benzotriazole-1-yl) -N, N, N ', N' -tetramethylurea tetrafluoroborate to triethylamine to the hydroxyplatinum compound 3 is 3:3:2.
  7. 7. The method of preparing a Zn/Co-MOF-based metal-organic framework nano-drug delivery platform according to claim 5, wherein step (2) specifically comprises the steps of: Zn (NO 3 ) 2 ·6H 2 O and Co (NO 3 ) 2 ·6H 2 O) are dissolved in methanol solution, then methanol dissolved with dimethyl imidazole is mixed into the methanol solution, the mixture is stirred and reacted, and the mixed solution is washed by methanol and is freeze-dried in vacuum, so that the Zn/Co-MOF nano particles are obtained.
  8. 8. The method for preparing a nano-drug delivery platform based on a metal organic framework of Zn/Co-MOF according to claim 5, wherein in the step (3), the Co-assembly process comprises dissolving tamoxifen-cisplatin dimer prodrug, photo-thermal therapeutic agent IR-820 and metformin in methanol, mixing and stirring with the Zn/Co-MOF nano-particles, centrifuging and washing, and drying to obtain drug-loaded nano-particles, wherein the mass ratio of tamoxifen-cisplatin dimer prodrug, photo-thermal therapeutic agent IR-820, metformin and Zn/Co-MOF nano-particles is 2:2:1:4.
  9. 9. The method for preparing a nano-drug delivery platform based on a metal organic framework of Zn/Co-MOF according to claim 5, wherein in the step (4), the liposome extrusion method is to mix MCF-7 cell membrane and the drug-loaded nano-particles in a phosphate buffer solution, repeatedly extrude the mixture through a liposome extruder, wherein the MCF-7 cell membrane is prepared by extracting MCF-7 cells with a cell density of 10 7 cells/mL, and the mass ratio of the MCF-7 cell membrane to the drug-loaded nano-particles is 1:1.
  10. 10. Use of a Zn/Co-MOF-based metal-organic framework nano-drug delivery platform as defined in any one of claims 1 to 4 in the manufacture of a medicament for the treatment of er+ breast cancer.

Description

Nano medicine delivery platform based on Zn/Co-MOF metal organic framework, and preparation method and application thereof Technical Field The invention belongs to the technical field of biology and new medicines, and particularly relates to a Zn/Co-MOF-based nano-drug delivery platform with a metal organic framework, a preparation method and application thereof. Background Tumors are novel organisms formed by abnormal proliferation and differentiation due to the fact that local tissue cells lose normal regulation at the gene level due to various tumorigenic factors. Malignant tumor growth can destroy normal tissues and organs and transfer to various parts of the body, so that serious organ function damage is caused, and human health is seriously threatened. The incidence and mortality of cancer rise year by year, resulting in mortality rates inferior to cardiovascular and cerebrovascular diseases, the second world. Global cancer data shows that by 2025, the number of new cancer cases worldwide will be up to 1930 ten thousand per year. Breast cancer is the most common cancer in women, and it is estimated that 230 tens of thousands of deaths are more than 68.5 tens of thousands in 2020. Although survival has increased significantly over the past two decades, the incidence of breast cancer continues to rise worldwide. The improvement in breast cancer treatment outcome is largely due to mammography and adjuvant therapy, however, efficient systemic therapy for advanced breast cancer patients is producing a significant impact. Cancer consists of multiple biological entities characterized by pathology, genomic changes, gene expression, and heterogeneity of tumor microenvironment, which together affect clinical behavior and therapeutic response. Currently, there are three main conventional approaches for clinically treating cancer, surgical excision therapy, radiation therapy, and chemotherapy. These methods have important roles in tumor treatment, inhibit further progression of some tumors, but also have limitations. Surgical excision therapy is the first choice therapy in early stage, but has the risk of recurrence or metastasis after operation, radiation therapy has great harm to the body, chemotherapy is generally suitable for adjuvant therapy, and clinically common medicines for treating tumors are of two types, namely traditional cytotoxic medicines and new molecular targeting medicines. Traditional cytotoxicity drugs mainly act on cell mitosis, DNA synthesis, repair and the like, but have low selectivity and large toxic and side effects because of nonspecific inhibition of cell division, and tumor cells are easy to generate drug resistance. Thus, there is an urgent need for effective and low-toxicity cancer therapies. Breast tumors are clinically divided into three major clinical groups, er+, her2+ and Triple Negative Breast Cancer (TNBC) er+ cancers accounting for about 70% of all breast cancers, based on the expression of Estrogen Receptor (ER), progestin Receptor (PR) and human epithelial growth factor receptor 2 (HER 2/ERBB 2), where er+ is defined as ≡1% ER positive tumor cells. The data in clinical treatment show that ER+ breast cancer is mainly treated by combined chemotherapy and endocrine therapy, but the resistance of ER+ breast cancer to combined chemotherapy and endocrine therapy is obvious at present, and the problems of drug resistance and synergistic chemotherapy are important. Metformin (Metformin) has been demonstrated in many literature to exert an immunotherapeutic effect on modulating immunity, and also to mediate the iron death pathway to exert an anticancer effect, and many have been used in anticancer development, but there are few cases of use in combination with endocrine therapy. Tamoxifen (tamoxifen) is used as the first targeted therapy for breast cancer, has been the gold standard for treating estrogen receptor positive breast cancer for nearly 50 years, and is widely used for treating hormone receptor positive breast cancer due to the advantages of safe use, definite curative effect, low cost, better tolerance and the like. ER is considered a nuclear transcription factor that can bind to estrogens or antiestrogenic compounds to cause or block replication of breast cancer cells. Disclosure of Invention In order to solve the technical problems, the invention provides a nano-drug delivery platform based on a Zn/Co-MOF metal organic framework, and a preparation method and application thereof. In order to achieve the above purpose, the present invention provides the following technical solutions: The invention provides a nano-drug delivery platform based on a Zn/Co-MOF metal organic framework, which comprises a Zn/Co-MOF metal organic framework core, an organic drug composition loaded on the surface and micropores of the core and a homologous tumor cell membrane wrapped on the outermost layer; wherein the organic pharmaceutical composition comprises tamoxifen-cisplatin dimer prodrug